CDK1 Subfamily (CDK1, CDK2 & CDK3)

The CDK1 subfamily includes CDK1, CDK2 and CDK3, all of which are innately involved in regulation and progression of the cell cycle. CDK1 binds to cyclin A or B and is critical during S and G2 phase, while CDK2 binds cyclin E and functions as a checkpoint control protein during G1/S phase. Inhibition of CDK1 or CDK2 leads to cell cycle arrest and apoptosis.


CDK1 Subfamily Inhibitors

Cat. No. Product Name / Activity
5472 CGP 74514 dihydrochloride
Potent CDK1 inhibitor
7336 Dinaciclib
Potent and selective inhibitor of CDK2, CDK5, CDK1 and CDK9
6789 K 03861
Potent CDK2 inhibitor
3301 NU 6140
Cdk2 inhibitor; also potent inhibitor of aurora kinase A and B
4181 Ro 3306
Cdk1 inhibitor
8031 RP 6306
Potent and selective PKMYT1 inhibitor
7192 SMIP 004
CDK2 inhibitor; also S-phase kinase-associated protein 2 (SKP2) inhibitor


Cat. No. Product Name / Activity
7800 CPS2
Potent and selective CDK2 Degrader (PROTAC®)


Cat. No. Product Name / Activity
1867 NSC 663284
Blocks cdk1 & cdk2 activation; Cdc25 phosphatase inhibitor

The CDK1 subfamily of cyclin-dependent kinases includes CDK1, CDK2 and CDK3. All three members of this family can bind cyclin A, cyclin B, cyclin E and possibly cyclin C, and are fundamentally involved in regulation of the cell cycle.


CDK1 is a 34kDa protein that is highly conserved and is essential for cell cycle progression in mammals. The roles of CDK2 and CDK3 in the cell cycle are dispensable as CDK1 can interact with multiple different cyclins to compensate if CDK2 and/or CDK3 are not present. Following DNA replication in S phase of the cell cycle, CDK1 is activated by binding to cyclin A or B, promoting chromosome condensation and centrosome maturation required for mitotic progression. Ablation of CDK1 in mouse models results in early embryonic lethality, indicating the vital role for CDK1 in embryonic development.

CDK1 activity is inhibited by WEE1-mediated inhibitory phosphorylation, while the Cdc25 family of phosphatases catalyzes phosphate group removal. Inhibition of Cdc25 maintains inhibition of CDK1; NSC 663284 (Cat. No. 1867) is a potent and selective Cdc25 inhibitor, which prevents activation of CDK1 and arrests the cell cycle at G1 and G2/M phase. Ro 3006 (Cat. No. 4181) is a potent CDK1 inhibitor that suppresses the activity for CDK1/cyclin B1 and CDK1/cyclin A, and induces G2/M phase cell cycle arrest and apoptosis in vitro.


CDK2 is involved in the inactivation of retinoblastoma protein (Rb) during the cell cycle, and de-repression of cell cycle related genes, but it also has additional functions within DNA repair and replication. The activity of CDK2 is restricted to G1/S phase of the cell cycle and it is known as a checkpoint control protein. CDK2 bound to cyclin E plays the same role as CDK4/6 bound to cyclin A in the cell cycle, although CDK2 is thought to activate a wider range of proteins than CDK4/6.

Due to the similarities between the active sites of CDK1 and CDK2, selective CDK2 inhibitors are hard to develop. Some success has been achieved by targeting CDK2 in its unbound state, or by targeting an allosteric binding site on CDK2, near the C-terminal helices. K 03861 (Cat. No. 6789), also known as AUZ 454, is a potent CDK2 inhibitor that inhibits both wild type and mutated CDK2. It competes with cyclin binding to inhibit CDK2 kinase activity in vitro.

Structure of CDK2 bound to cyclin A

Figure 1: 3D structure of CDK2 (green) bound to Cyclin A (orange). Taken from Wood et al (2019) Differences in the Conformational Energy Landscape of CDK1 and CDK2 Suggest a Mechanism for Achieving Selective CDK Inhibition. Cell Chem Biol. 26, 121. PMID: 30472117


CDK3 is involved in G0 to G1 and G1/S phases of the cell cycle, where it interacts with cyclin C to phosphorylate targets including histone H1 and the transcription factor ATF1. ATF1 phosphorylation triggers its translocation and activation of transcription and promotes cell proliferation and translocation. Endogenous inactivating mutations in CDK3 identified in mice suggest that the role of CDK3 in the cell cycle is not essential, and that loss of CDK3 can be compensated for by other CDKs.